Single-Cell Analysis Uncovers Striking Cellular Heterogeneity of Lung-Infiltrating Regulatory T Cells during Eosinophilic versus Neutrophilic Allergic Airway Inflammation.

Allergic airway inflammation results from uncontrolled immune responses to environmental Ags. Although it is well established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types such as eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the mechanisms responsible for such pathogenesis remain elusive. Foxp3+ regulatory T cells (Tregs) are essential immune regulators during chronic inflammation, including allergic airway inflammation. Emerging evidence suggests that Tregs infiltrating inflamed tissues exhibit distinct phenotypes dependent on the specific tissue sites and can display heterogeneity and tissue residency. Whether diverse allergic airway inflammatory responses influence infiltrating Treg heterogeneity or Treg lung residency has not been explored. We employed an unbiased single-cell RNA sequencing approach to investigate lung-infiltrating Tregs in models of eosinophilic and neutrophilic airway inflammation. We found that lung-infiltrating Tregs are highly heterogeneous, and that Tregs displaying lung-resident phenotypes are significantly different depending on the types of inflammation. Treg expression of ST2, a receptor for alarmin IL-33, was predominantly associated with eosinophilic inflammation and tissue residency. Nevertheless, Treg-specific ST2 deficiency did not affect the development of eosinophilic allergic inflammation or the generation of lung-resident Tregs. These results uncover a stark heterogeneity among Tregs infiltrating the lungs during allergic airway inflammation. The results indicate that varying types of inflammation may give rise to phenotypically distinct lung-resident Tregs, underscoring a (to our knowledge) novel mechanism by which inflammatory cues may shape the composition of infiltrating Tregs, allowing them to regulate inflammatory responses through tissue-adapted mechanisms.

Utilizing CaCl2 to promote the enrichment and bioavailability of phosphorus in incinerated sludge ash.

Recovering phosphorus from incineration sludge sewage ash (ISSA) is a well-established technology, with a greater recovery potential than that of supernatant or sludge. ISSA can be utilized as a secondary raw material in the fertilizer industry, or as a fertilizer if heavy metal concentrations do not exceed permissible limits, thus reducing the cost of phosphorus recovery. Increasing the temperature to produce ISSA with higher solubility and plant availability of phosphorus is advantageous for both pathways. But a decrease in the extraction of phosphorus is also observed at high temperatures, thereby diminishing the overall economic benefits. In this study, CaCl2 was utilized to mitigate the decrease in the extraction rate and also to promote the bioavailability of phosphorus. The addition of CaCl2 (80 g/kg of dry sludge) effectively promoted the conversion of non-apatite inorganic phosphorus to apatite inorganic phosphorus at a rate of 87.73% at 750 °C. Furthermore, the decrease in the extraction rate of phosphorus at 1,050 °C was comparatively smaller in the presence of CaCl2. If iron flocculants are used to capture P in wastewater management, it may be necessary to pay special attention to the amount of addition and incineration temperature to maximize the economic potential of recycling.

Lymphocyte activation gene 3 (Lag3) supports Foxp3 + Treg cell function by restraining c-Myc-dependent aerobic glycolysis.

Lymphocyte activation gene 3 (Lag3) has emerged as the next-generation immune checkpoint molecule due to its ability to inhibit effector T cell activity. Foxp3 + regulatory T (Treg) cells, a master regulator of immunity and tolerance, also highly express Lag3. While Lag3 is thought to be necessary for Treg cell-mediated regulation of immunity, the precise roles and underlying mechanisms remain largely elusive. In this study, we report that Lag3 is indispensable for Treg cells to control autoimmune inflammation. Utilizing a newly generated Treg cell specific Lag3 mutant mouse model, we found that these animals are highly susceptible to autoimmune diseases, suggesting defective Treg cell function. Genome wide transcriptome analysis further uncovered that Lag3 mutant Treg cells upregulated genes involved in metabolic processes. Mechanistically, we found that Lag3 limits Treg cell expression of Myc, a key regulator of aerobic glycolysis. We further found that Lag3-dependent Myc expression determines Treg cells’ metabolic programming as well as the in vivo function to suppress autoimmune inflammation. Taken together, our results uncovered a novel function of Lag3 in supporting Treg cell suppressive function by regulating Myc-dependent metabolic programming.

Effect of Corn Straw Blending on Phosphorus Specification and Bioavailability of Incinerated Sludge Ash.

Phosphorus is a depletable resource, and the consumption of phosphorus fertilizer increases with the growing population size. Phosphorus recycled from incinerated sludge ash can be a complement to phosphatic fertilizers in districts suffering from phosphorus resource shortages (e.g., Germany, Japan, and Sweden). The apatite inorganic phosphorus (AP) content in incinerated sludge ash is a key factor influencing the recoverability and bioavailability. Biomass straw is rich in calcium and magnesium minerals and can be used as an additive to be blended with sludge to increase the AP content. However, most of the current studies added excessive amounts of calcium-based or biomass additives, and the bioavailability of various Ca-Mg-P minerals generated after the addition of biomass has not been systematically discussed. In this study, the changes of the phosphorus form in the mixed sludge and biomass with Ca/P in the range of 1.0-2.5 are studied, and the influence of temperature and additives on the phosphorus form and the bioavailability of phosphorus in the ash samples are discussed by combining X-ray diffraction and citric acid (CA) leaching experiments. The AP content is very low in the residue of the sludge or corn straw (CS) that has been burned individually. The sludge and the blended sludge and CS were incinerated at various temperatures. As the incineration temperature increased, the conversion of non-apatite inorganic phosphorus (NAIP) to AP was promoted, but the bioavailability did not change until 1050 °C for samples with a Ca/P of 2.5. In the range from 750 to 950 °C, higher temperature promotes the formation of Ca2P2O7 and CaP2O6. CaP2O6 is insoluble in CA; thus, the bioavailability changes little from 750 to 950 °C, although the AP content increases. With the increase of Ca/P, the conversion of NAIP to AP and the bioavailability of phosphorus were promoted. For the blended sludge and CS ash, Ca7Mg2P6O24 appears at 950 and 1050 °C and the bioavailability also increases.

Organic removal from coal-to-chemical brine by a multistage system of adsorption-regeneration and electrochemically driven UV/chlorine processes.

Treatment of coal-to-gas brine (CGB) is a great challenge since it contains elevated inorganic salts and a high level of toxic and bio-accumulative organics. In this study, CGB treatment was conducted by adsorptionregeneration and electrochemically driven UV/chlorine (E-UV/Cl2) processes. LS-109D macroporous resin was optimal adsorbent primarily due to unique pore structure, which preferably adsorbed the aromatic fluorescent components with quenching Cl∙ effect and low molecular weight acids recalcitrant to ∙OH. The E-UV/Cl2 process outperformed the UV photolysis process and electrochemical advanced oxidation processes (EAOPs) for oxidation of organic compounds due to its full utilization of Cl- in CGB to produce highly active oxidation agents. Thanks to the synergy between process units in organic matter removal, dissolved organic carbon (DOC) of CGB was reduced from 163.41 mg/L to 26.58 mg/L by the multistage system. Furthermore, the CGB with characteristics of high fluorescence and molecular weight (MW) distribution was converted to effluent with low fluorescence and MW distribution. The exhausted LS-109D was regenerated by ultrasound-assisted hot water elution at 363 K. After pretreated by ozonation, the eluate can be easily treated by biological process. The study suggests that the multistage system can provide an effective treatment option for removing organics from CGB.

Vaccine with bacterium-like particles displaying HIV-1 gp120 trimer elicits specific mucosal responses and neutralizing antibodies in rhesus macaques.

Preclinical studies have shown that the induction of secretory IgA (sIgA) in mucosa and neutralizing antibodies (NAbs) in sera is essential for designing vaccines that can effectively block the transmission of HIV-1. We previously showed that a vaccine consisting of bacterium-like particles (BLPs) displaying Protan-gp120AE-MTQ (PAM) could induce mucosal immune responses through intranasal (IN) immunization in mice and NAbs through intramuscular (IM) immunization in guinea pigs. Here, we evaluated the ability of this vaccine BLP-PAM to elicit HIV-1-specific mucosal and systemic immune responses through IN and IM immunization combination strategies in rhesus macaques. First, the morphology, antigenicity and epitope accessibility of the vaccine were analysed by transmission electron microscopy, bio-layer interferometry and ELISA. In BLP-PAM-immunized macaques, HIV-1-specific sIgA were rapidly induced through IN immunization in situ and distant mucosal sites, although the immune responses are relatively weak. Furthermore, the HIV-1-specific IgG and IgA antibody levels in mucosal secretions were enhanced and maintained, while production of serum NAbs against heterologous HIV-1 tier 1 and 2 pseudoviruses was elicited after IM boost. Additionally, situ mucosal responses and systemic T cell immune responses were improved by rAd2-gp120AE boost immunization via the IN and IM routes. These results suggested that BLP-based delivery in combination with the IN and IM immunization approach represents a potential vaccine strategy against HIV-1.